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Title:Patient-derived tumor organoids mimic treatment-induced DNA damage response in glioblastoma
Authors:ID Majc, Bernarda (Author)
ID Habič, Anamarija (Author)
ID Malavolta, Marta (Author)
ID Vittori, Miloš (Author)
ID Porčnik, Andrej (Author)
ID Bošnjak, Roman (Author)
ID Mlakar, Jernej (Author)
ID Matjašič, Alenka (Author)
ID Zupan, Andrej (Author)
ID Skoblar Vidmar, Marija (Author)
ID Lah Turnšek, Tamara (Author)
ID Sadikov, Aleksander (Author)
ID Breznik, Barbara (Author)
ID Novak, Metka (Author)
Files:URL URL - Source URL, visit https://doi.org/10.1016/j.isci.2024.110604
 
.pdf PDF - Presentation file, download (9,14 MB)
MD5: 220C2B909461DA4CB74BE4BD247ADC6C
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo NIB - National Institute of Biology
Abstract:Glioblastoma (GB) is the most common primary malignant brain tumor, characterized by resistance to therapy. Despite aggressive treatment options, GB remains an incurable disease. Invasiveness and heterogeneity are key GB features that cannot be studied in preclinical in vitro models. In this study, we investigated the effects of standard therapy using patient-derived GB organoids (GBOs). GBOs reflect the complexity and heterogeneity of the original tumor tissue. No significant effect on GBO viability or invasion was observed after irradiation and temozolomide treatment. E3 ubiquitin-protein ligase (MDM2), cyclin-dependent kinase inhibitor 1A (CDKN1A), and the serine/threonine kinases ATM and ATR were upregulated at the gene and protein levels after treatment. Our results show that the p53 pathway and DNA-damage response mechanisms were triggered, suggesting that GBOs recapitulate GB therapy resistance. GBOs thus provide a highly efficient platform to assess the specific responses of GB patients to therapy and to further explore therapy resistance.
Keywords:cellular physiology, cellular toxicology, in vitro toxicology including 3D culture, technical aspects of cell biology, cancer
Publication status:Published
Publication version:Version of Record
Publication date:20.09.2024
Year of publishing:2024
Number of pages:str. 1-19
Numbering:iss. 9, [art. no.] ǂ110604
PID:20.500.12556/DiRROS-20412 New window
UDC:576
ISSN on article:2589-0042
DOI:10.1016/j.isci.2024.110604 New window
COBISS.SI-ID:205414147 New window
Note:Soavtorji: Anamarija Habič, Marta Malavolta, Miloš Vittori, Andrej Porčnik, Roman Bošnjak, Jernej Mlakar, Alenka Matjašič, Andrej Zupan, Marija Skoblar Vidmar, Tamara Lah Turnšek, Aleksander Sadikov, Barbara Breznik, Metka Novak; Nasl. z nasl. zaslona; Opis vira z dne 27. 8. 2024;
Publication date in DiRROS:09.09.2024
Views:353
Downloads:163
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Record is a part of a journal

Title:iScience
Publisher:Cell Press, Elsevier
ISSN:2589-0042
COBISS.SI-ID:24098568 New window

Document is financed by a project

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P1-0245-2019
Name:Ekotoksiologija, toksikološka genomika in karcinogeneza

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:J3-4504-2022
Name:Z vizualizacijo mikrookolja glioblastoma do boljše terapije

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:J3-2526-2020
Name:Razkrivanje niše matičnih glioma celic v iskanju novih terapevtskih ciljev pri bolnikih z glioblastomom

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:NC-0023-2022
Name:Inovativne sonde in inhibicija metaloproteaz za ciljanje glioblastomskih matičnih celic v tumorskem mikrooklju

Funder:EC - European Commission
Project number:101079113
Name:TWINNING FOR EXCELLENCE TO STRATEGICALLY ADVANCE RESEARCH IN CARCINOGENESIS AND CANCER
Acronym:CutCancer

Funder:EC - European Commission
Project number:956394
Name:PremAtuRe nEwborn motor and cogNitive impairmenTs: Early diagnosis
Acronym:PARENT

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P2-0209-2022
Name:Umetna inteligenca in inteligentni sistemi

Funder:ARIS - Slovenian Research and Innovation Agency
Funding programme:Young researcher grants
Project number:10040137 and 10040147

Funder:EC - European Commission
Funding programme:European Program of Cross-Border Cooperation for Slovenia-Italy Interreg
Name:TRANS-GLIOMA

Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

Language:Slovenian
Keywords:glioblastom, organoidi, monoterpeni, rak, onkologija, celična fiziologija, celična toksikologija, celična biologija, toksikologija in vitro


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